This investigation will continue the localization of the biogenic amines (BA), donamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5HT) at the electron microscopic level. Techniques for these biogenic amines have been developed by the principal investigator. Recent refinements in methodology have increased the sensitivity of all procedures and these methods have been successfully used at the light, as well as the electron microscopic level. Light microscopic results correlate with fluorescent methods. The simplicity and ease of use of the new methodology is valuable to this laboratory and to other laboratories working in similar areas. The heavy metal methods in use have been confirmed by in vitro studies as well as by X-ray analysis. Definite differentiation of NE and DA from 5HT has been accomplished at the light and electron microscopic levels. Nerve cell bodies as well as terminals have been shown to contain amines and positive reactive sites will be studied as to synthesis, as well as storage and release. Attempts are being continued to perfect a method for differentiating NE from DA and investigations have shown that modifications in procedure can retain more deposits than had been done previously. Enzymes related to adrenergic function are being studied using the adrenal medulla as a model at the histological, histochemical, cytochemical and biochemical levels. Drugs which selectively release, block and destroy biogenic amine sites will be studied as will amine precursors.